It is possible to modify the trial protocol to examine other medicines.
The National Institutes of Health has begun a multi-site clinical trial to evaluate an experimental antiviral for the treatment of COVID-19. Hokkaido University in Sapporo, Japan, and Shionogi & Co., Ltd. in Osaka, Japan, found S-217622 or ensitrelvir fumaric acid as a treatment for cancer. The trial will enroll around 1,500 individuals at sites throughout the world to see whether S-217622 can enhance clinical outcomes for hospitalized COVID-19 patients in comparison to a placebo. S-217622 is the first medication to be assessed in a new adaptive global clinical research protocol titled Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE).
The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) is supporting the trial and collaborating with the National Center for Advancing Translational Sciences of the NIH (NCATS). STRIVE, which was developed under the auspices of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, can be used to rapidly assess various therapeutic interventions during outbreaks of respiratory diseases such as COVID-19 or influenza.
Dr. H. Clifford Lane, M.D., Deputy Director for Clinical Research and Special Projects at the National Institutes of Allergy and Infectious Diseases, stated, “We hope that the results of this trial can be used to improve the standard of care for people with COVID-19, which continues to cause hundreds of deaths per day in the United States, and to strengthen our pandemic preparedness.” The STRIVE procedure and clinical research infrastructure can be modified to investigate other medicines for COVID-19 and other respiratory infections.
Findings from the ACTIV-3 studies, which examined therapies for adults hospitalized with COVID-19, suggested that continuing viral replication may play a role in the progression of disease to critical illness. The research team predicted that a substantial number of hospitalized COVID-19 patients could still benefit from antiviral treatment.
S-217622 reduces SARS-CoV-2 replication by decreasing the activity of 3CL protease, a crucial viral enzyme. The antiviral reduced COVID-19 symptoms in individuals with mild-to-moderate COVID-19, regardless of risk factors or vaccination status, according to data from a Phase 3 clinical trial conducted mostly in Japan and shared by Shionogi. S-217622 was well tolerated, and there were no significant adverse events or deaths connected to therapy in the research. The medicine obtained emergency regulatory approval in Japan in November 2022, where it is marketed under the brand name Xocova. NIAID is also funding the ongoing ACTIV-2 SCORPIO-HR clinical trial, which is investigating the antiviral in outpatients.
The trial chair is Dr. Jason Baker, chief of infectious diseases at Hennepin Healthcare and associate professor of medicine at the University of Minnesota, Minneapolis. Trial co-chairs include Marcelo Losso, M.D., principal investigator at Hospital J.M. Ramos Mejia in Buenos Aires, Argentina, and director of Latin America Coordination of Academic Clinical Research, Buenos Aires; and Shikha Vasudeva, M.D., assistant professor of medicine at the Virginia Tech Carilion School of Medicine in Roanoke and infectious disease specialist at the Department of Veterans Affairs Medical Center in Salem, Virginia.
Random assignment will determine whether participants get S-217622 or a placebo. Neither the researchers nor the volunteers will be aware of who is receiving the investigational medication. S-217622 is administered orally once every day for five days. Three 125 milligram (mg) pills are taken on the first day for a total of 375 mg, followed by one 125 mg tablet per day for the next four days. All patients will receive the local standard of care for COVID-19, which may vary by location and may include of an additional antiviral, immunomodulatory medications, corticosteroids, and/or anticoagulants.
Researchers will monitor and record the health status of participants daily for the first week, and then on predetermined days for the next 60 days. Participants will also be required to contribute blood and nasal swabs for laboratory testing.
The research team will analyze any statistically significant changes between the treatment group and the placebo group, i.e., those that are unlikely to be due to chance. The primary metric will be whether individuals receiving S-217622 recover faster than those receiving a placebo (defined as returning home and being alive until day 60).
The safety of the participants will be constantly checked during the duration of the trial. An NIAID Medical Monitor will assess any potential safety concerns in real-time, and an independent data and safety monitoring board (DSMB) will frequently review safety and efficacy data.
The rate of enrolment and, eventually, the duration of the trial will rely on the progression of COVID-19 cases in different regions of the world. Please visit clinicaltrials.gov and enter the identifier NCT05605093 for more information about the trial.
STRIVE is a component of the NIH ACTIV public-private partnership, which was launched in April 2020 to build a coordinated research strategy for selecting and accelerating the development of COVID-19’s most promising therapies and vaccines. STRIVE draws on previous ACTIV master protocols that examined multiple treatments for COVID-19 patients hospitalized in the hospital. The STRIVE Scientific Committee, chaired by Professor Jens Lundgren, M.D., of the University of Copenhagen, consists of clinical trial experts from a variety of medical disciplines, including infectious diseases, pulmonology, critical care, and emergency medicine. A leadership council and a community advisory board also monitor STRIVE.
The University of Minnesota’s Statistical and Data Management Center, directed by James Neaton, Ph.D., manages STRIVE in partnership with eight foreign coordinating centers, bringing together previous ACTIV-1, ACTIV-3, and ACTIV-5 clinical trial sites. STRIVE may enroll individuals at over 200 locations on each of the six inhabited continents.
NIAID conducts and funds research at NIH, throughout the United States, and internationally to investigate the causes of infectious and immune-mediated disorders and to create better methods for preventing, detecting, and treating them. On the NIAID website, you can find press releases, fact sheets, and other relevant information.
NIH stands for the National Institutes of Health. The National Institutes of Health (NIH), the nation’s medical research organization, consists of 27 Institutes and Centers and is part of the U.S. Department of Health and Human Services. The NIH is the principal government organization that conducts and supports basic, clinical, and translational medical research and investigates the causes, treatments, and cures for both common and rare diseases. Visit www.nih.gov for more information on the NIH and its initiatives.
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